@article{defe9edd8ad346c88eb4141d5145a007,
title = "Detailed mapping of behavior reveals the formation of prelimbic neural ensembles across operant learning",
abstract = "The prelimbic cortex (PrL) is involved in the organization of operant behaviors, but the relationship between longitudinal PrL neural activity and operant learning and performance is unknown. Here, we developed deep behavior mapping (DBM) to identify behavioral microstates in video recordings. We combined DBM with longitudinal calcium imaging to quantify behavioral tuning in PrL neurons as mice learned an operant task. We found that a subset of PrL neurons were strongly tuned to highly specific behavioral microstates, both task and non-task related. Overlapping neural ensembles were tiled across consecutive microstates in the response-reinforcer sequence, forming a continuous map. As mice learned the operant task, weakly tuned neurons were recruited into new ensembles, with a bias toward behaviors similar to their initial tuning. In summary, our data suggest that the PrL contains neural ensembles that jointly encode a map of behavioral states that is fine grained, is continuous, and grows during operant learning.",
keywords = "behavioral sequence, behavioral tuning, cognitive maps, deep behavior mapping, learning, longitudinal calcium imaging, miniScope, neural ensembles, operant conditioning, prelimbic cortex",
author = "Yan Zhang and Denman, {Alexander J.} and Bo Liang and Werner, {Craig T.} and Beacher, {Nicholas J.} and Rong Chen and Yun Li and Yavin Shaham and Giovanni Barbera and Lin, {Da Ting}",
note = "Funding Information: We thank the Genetically-Encoded Neuronal Indicator and Effector (GENIE) Project and the Janelia Research Campus of the Howard Hughes Medical Institute (HHMI) for generously allowing the use of GCaMP6 in our research. We thank the Machine Learning Team of National Institute of Mental Health Intramural Research Program (NIMH IRP) for their consultation in optimizing our DBM algorithm. This work used the computational resources of the NIH HPC Biowulf cluster (http://hpc.nih.gov). We thank Drs. Geoffrey Schoenbaum and Bruno Averbeck for critical reading of the manuscript. Research was supported by NIH/NIDA/IRP. Y.Z. N.J.B. and C.T.W. are supported by a postdoctoral fellowship from the Center on Compulsive Behaviors, National Institutes of Health. Y.L. is supported by NIGMS COBRE 5P20GM121310. D.-T.L. G.B. Y.S. Y.L. B.L. and Y.Z. conceptualized the project. B.L. G.B. and Y.Z. constructed the experimental setup and built the custom imaging system. Y.Z. performed all experiments. G.B. performed some initial pilot data analysis. A.J.D. developed the DBM method and performed most data analysis. R.C. contributed important intellectual input in the statistical analysis. C.T.W. N.J.B. Y.L. and Y.S. contributed critical intellectual input throughout the project. D.-T.L. supervised the project. All authors contributed to the writing of the manuscript. The authors declare no competing interests. Funding Information: We thank the Genetically-Encoded Neuronal Indicator and Effector (GENIE) Project and the Janelia Research Campus of the Howard Hughes Medical Institute (HHMI) for generously allowing the use of GCaMP6 in our research. We thank the Machine Learning Team of National Institute of Mental Health Intramural Research Program (NIMH IRP) for their consultation in optimizing our DBM algorithm. This work used the computational resources of the NIH HPC Biowulf cluster ( http://hpc.nih.gov ). We thank Drs. Geoffrey Schoenbaum and Bruno Averbeck for critical reading of the manuscript. Research was supported by NIH/NIDA/IRP . Y.Z., N.J.B., and C.T.W. are supported by a postdoctoral fellowship from the Center on Compulsive Behaviors, National Institutes of Health . Y.L. is supported by NIGMS COBRE 5P20GM121310 . Publisher Copyright: {\textcopyright} 2021",
year = "2022",
month = feb,
day = "16",
doi = "10.1016/j.neuron.2021.11.022",
language = "English",
volume = "110",
pages = "674--685.e6",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "4",
}